The anti-cancer activity of cis Pt(NH.sub.3).sub.2 Cl.sub.2 is well documented and, is believed to result not from prevention of DNA replication but from damage to the DNA producing faulty replication. Damaged DNA is repaired by various DNA repair enzymes. It thus follows that if an agent such as cis Pt(NH.sub.3).sub.2 Cl.sub.2 which damages DNA is administered along with another agent which inhibits a DNA repair enzyme, then the kill of cancerous cells will be greatly enhanced.
Caffeine is an inhibitor of DNA repair and it has been shown in cell culture studies that caffeine greatly increases cell kill caused by cis Pt(NH.sub.3).sub.2 Cl.sub.2. While these cell culture studies have been demonstrably successful in vitro, they have not been successfully replicated in vivo, i.e., no enhancement of anti-cancer activity occurs when these compounds are combined.
Relevant references describing the effect of the Pt(NH.sub.3).sub.2 Cl.sub.2 and caffeine are:
______________________________________ Author Title Number ______________________________________ Van Den Berg, Synergism Between the Anti- 75-4316 H. W. tumor Agent cis Platinum (II) Diamminedichloride and Caffeine: Toxicological and Molecular Studies (abstract) Van Den Berg, Post-Republican Repair of 76-4670 H. W. DNA in Chinese Hamster Cells Treated with Cis Platinum (II) Diamine Dichloride, Enhancement of Toxicity and Chromosome Damage by Caffeine ______________________________________
It was theorized that the difference between in vivo and in vitro reactions may have been due to solubility and membrane transport properties and that, if the caffeine molecule could be complexed in such a way that these properties would be enhanced, the successful anti-cancer composition could be produced.